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Mutations in the FPIV motif of Newcastle disease virus matrix protein attenuate virus replication and reduce virus budding

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Abstract

The FPIV-like late domains identified in the matrix (M) proteins of parainfluenza virus 5 and mumps virus have been demonstrated to be critical for virus budding. In this study, we found that the same FPIV sequence motif is present in the N-terminus of the Newcastle disease virus (NDV) M protein. Mutagenesis experiments demonstrated that mutation of either phenylalanine (F) or proline (P) to alanine led to a more obvious decrease in viral virulence and replication and resulted in poor budding of the mutant viruses. Additionally, evidence for the involvement of cellular multivesicular body (MVB) proteins was obtained, since NDV production was inhibited upon expression of dominant-negative versions of the VPS4A-E228Q protein. Together, these results demonstrate that the FPIV motif, especially the residues F and P, within the NDV M protein, plays a critical role in NDV replication and budding, and this budding process likely involves the cellular MVB pathway.

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Acknowledgments

We would like to thank Wes Sundquist (Department of Biochemistry, University of Utah) for providing plasmids encoding VPS4A proteins, and Dr. Chan Ding (Shanghai Veterinary Research Institute, China) for providing mouse anti-NDV NP monoclonal antibody (3F5). This work was supported by National Natural Science Foundation of China (31172338), a project funded by the Excellent Doctoral Dissertation of Yangzhou University, the Earmarked Fund for Modern Agro-industry Technology Research System (nycytx-41-G07), the Priority Academic Program Development of Jiangsu Higher Education Institutions, and the Chinese Special Fund for Agro-Scientific Research in the Public Interest (201303033).

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The authors have declared that no conflict of interest exists.

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Authors and Affiliations

  1. Animal Infectious Disease Laboratory, College of Veterinary Medicine, Yangzhou University, 12 East Wenhui Road, Yangzhou, 225009, Jiangsu, China

    Zhiqiang Duan, Zenglei Hu, Jie Zhu, Haixu Xu, Jian Chen, Huimou Liu, Shunlin Hu & Xiufan Liu

  2. Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, 225009, China

    Huimou Liu, Shunlin Hu & Xiufan Liu

  3. Ministry of Education Key Lab for Avian Preventive Medicine, Yangzhou University, Yangzhou, 225009, China

    Huimou Liu, Shunlin Hu & Xiufan Liu

Authors
  1. Zhiqiang Duan
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  2. Zenglei Hu
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  3. Jie Zhu
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  4. Haixu Xu
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  5. Jian Chen
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  6. Huimou Liu
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  7. Shunlin Hu
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  8. Xiufan Liu
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Corresponding author

Correspondence to Xiufan Liu.

Additional information

Z. Duan and Z. Hu contributed equally to this work.

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Duan, Z., Hu, Z., Zhu, J. et al. Mutations in the FPIV motif of Newcastle disease virus matrix protein attenuate virus replication and reduce virus budding. Arch Virol 159, 1813–1819 (2014). https://doi.org/10.1007/s00705-014-1998-2

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  • DOI: https://doi.org/10.1007/s00705-014-1998-2

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